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Biomedical subjects

R J Greene

Publications and source records attributed to R J Greene.

At least 19 recordsLinked to original sources
PubMed2000

Heptad-repeat regions of respiratory syncytial virus F1 protein form a six-membered coiled-coil complex.

The Respiratory Syncytial Virus (RSV) fusogenic glycoprotein F(1) was characterized using biochemical and biophysical techniques. Two heptad-repeat (HR) regions within F(1) were shown to interact. Proteinase-K digestion experiments highlight the HR1 region (located proximal to the fusion peptide sequence) of the F(1) protein to which an HR2-derived (located proximal to the membrane-spanning domain) peptide binds, thus protecting both the protein and peptide from digestion. Solution-phase analysis of HR1-derived peptides shows that these peptides adopt helical secondary structure as measured by circular dichroism. Sedimentation equilibrium studies indicate that these HR1 peptides self-associate in a monomer/trimer equilibrium with an association constant of 5.2 x 10(8) M(-2). In contrast, HR2-derived peptides form random monomers in solution. CD analysis of mixtures containing peptides from the two regions demonstrate their propensity to interact and form a very stable (T(m) = 87 degrees C), helical (86% helicity) complex comprised of three HR1 and three HR2 members.

Amino Acid Sequence↗
PubMed1999

Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs.

The focus of this study was to examine the influence of age and diet on various parameters of immune function in young and old Fox Terriers and Labrador Retrievers. Eighteen young and old dogs were utilized for this study. Young and old dogs were fed a basal diet containing an (n-6):(n-3) ratio of 25:1 for sixty days (Phase I). Half of the dogs were then switched to a diet with an (n-6):(n-3) ratio of 5:1, and all were maintained on their respective diets for an additional sixty days (Phase II). Results from these studies revealed an age-associated decline in several immune parameters measured. Both these breeds demonstrated a reduction in sheep red blood cell titers, as well as in their ability to respond to different mitogens. Interestingly, this decline was greater in Fox Terriers, suggesting a decrease in cellular proliferative capacity in lymphocytes isolated from the larger breed. Neither cytokine production or DTH response was affected by age. Diet and breed interactions resulted in a significant increase in T- and B-cell mitogen responsiveness. In contrast, supplementation with n-3 fatty acids did not affect IL-1, IL-6 or TNF-alpha production. Supplementation with n-3 fatty acids resulted in increased PGE3 production from peritoneal macrophages but had no effect on PGE2 production from peripheral blood mononuclear cells or peritoneal macrophages. The n-3 fatty acid supplementation did not influence alpha-tocopherol status although older dogs had significantly lower serum alpha-tocopherol concentrations. Oxidative status of these dogs was assessed by serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Feeding an n-3-enriched diet did not affect 4-HNE levels but significantly decreased MDA levels in old dogs. In summary, this study indicates that feeding a diet containing an (n-6):(n-3) fatty acid ratio of 5:1 had a positive, rather than a negative, effect on the immune response of young or geriatric dogs.

Aging↗
PubMed1998

Cost-effectiveness of coronary artery bypass surgery in octogenarians.

OBJECTIVE: The objective of this retrospective cohort study was to determine whether coronary artery bypass graft (CABG) surgery is effective and cost-effective relative to medical management of coronary artery disease (CAD) in the elderly. SUMMARY BACKGROUND DATA: The aging of the U.S population and the improvements in surgical techniques have resulted in increasing numbers of elderly patients who undergo this surgery. The three randomized, controlled trials (RCTs) that established the efficacy of CABG surgery completed patient enrollment from 19 to 24 years ago excluded patients older than 65 years. Although information regarding outcomes of CABG in this population is mainly available in case series, a major lacuna exists with respect to information on quality of life and cost effectiveness of surgery as compared with medical management. METHODS: The authors retrospectively formed surgical and medically managed cohorts of octogenarians with significant multivessel CAD. More than 600 medical records of patients older than 80 years who underwent angiography at our institution were reviewed to identify 48 patients who were considered reasonable surgical candidates but had not undergone surgery. This cohort was compared with 176 patients who underwent surgery. RESULTS: The cost per quality-adjusted life year saved was $10,424. At 3 years, survival in the surgical group was 80% as compared with 64% in the entire medical cohort and 50% in a smaller subset of the medical cohort. Quality of life in patients who underwent surgery was measurably better than that of the medical cohort with utility index scores, as measured by the EuroQoL, (a seven-item quality of life questionnaire) of 0.84, 0.61, and 0.74, respectively. CONCLUSIONS: Performing CABG surgery in octogenarians is highly cost-effective. The quality of life of the elderly who elect to undergo CABG surgery is greater than that of their cohorts and equal to that of an average 55-year-old person in the general population.

Age Factors↗
PubMed1996

Interprofessional clinical education of medical and pharmacy students.

Pharmacists have become increasingly involved in influencing prescribing. Pharmaceutical education has changed accordingly, with increased teaching in therapeutics, partly on hospitals wards, giving students an insight into diseases and helping communication with clinicians. To extend this idea we have designed joint therapeutics teaching sessions with pharmacy and medical students. The scheme involves final year pharmacy students who have completed a course in clinical pharmacy and medical students who have completed their second MB. Interdisciplinary pairs of students are assigned a patient with common medical and therapeutic problems, such as arthritis, diabetes and cardiac failure; patients on multiple drug treatments are preferred. They jointly obtain a history: the medical student performs basic clerking, while the pharmacy student obtains the medication history. The medical student subsequently presents a brief medical history, with a summary of the patient's current problems. For each problem, the pharmacy student presents the current therapy, its rationale and how it is to be monitored. Experience with 73 students over 3 years has shown that almost all found sessions with students from another discipline useful. Few felt that members of the pairs contributed unequally. The main problem appeared to be insufficient time (although 2 1/2 h were allowed). Most students favoured more such sessions. Little difference in ability appeared between the two disciplines; there was considerable co-operation and little nascent 'professional rivalry'. The medical students were more comfortable interviewing patients, and the pharmacy students more confident analysing drug therapy. It is concluded that such interdisciplinary sessions are a successful method of clinical teaching and should be encouraged.

Drug Therapy↗
PubMed1993

Variability of physiologically based pharmacokinetic (PBPK) model parameters and their effects on PBPK model predictions in a risk assessment for perchloroethylene (PCE).

When used in the risk assessment process, the output from physiologically based pharmacokinetic (PBPK) models has usually been considered as an exact estimate of dose, ignoring uncertainties in the parameter values used in the model and their impact on model predictions. We have collected experimental data on the variability of key parameters in a PBPK model for tetrachloroethylene (PCE) and have used Monte Carlo analysis to estimate the resulting variability in the model predictions. Blood/air and tissue/blood partition coefficients and the interanimal variability of these data were determined for tetrachloroethylene (PCE). The mean values and variability for these and other published model parameters were incorporated into a PBPK model for PCE and a Monte Carlo analysis (n = 600) was performed to determine the effect on model predicted dose surrogates for a PCE risk assessment. For a typical dose surrogate, area under the blood time curve for metabolite in the liver (AUCLM), the coefficient of variation was 25% and the mean value for AUCLM was within a factor of two of the maximum and minimum values generated in the 600 simulations. These calculations demonstrate that parameter uncertainty is not a significant potential source of variability in the use of PBPK models in risk assessment. However, we did not in this study consider uncertainties as to metabolic pathways, mechanism of carcinogenicity, or appropriateness of dose surrogates.

Administration, Inhalation↗
PubMed1992

Structural determination of the carboxylic acid metabolites of polychlorotrifluoroethylene.

1. Polychlorotrifluoroethylene (PCTFE) is a perhalogenated hydrocarbon which consists mainly of C-6 and C-8 oligomers of chlorotrifluoroethylene (CTFE) end-capped with chlorine and referred to as trimer and tetramer, respectively. PCTFE is a hydraulic fluid considered for use in advanced weapon systems. 2. Inhalation studies have shown that PCTFE causes a dose-related hepatotoxicity in rats that is accompanied by proliferation of hepatic peroxisomes and increased liver weight. 3. Carboxylic acid metabolites of PCTFE have been isolated from rats exposed to PCTFE via inhalation. These metabolites, or their formation, may be involved in the toxicity of PCTFE. 4. Trimer carboxylic acids have been isolated from rat urine and identified, and tetramer carboxylic acids have been isolated from rat liver, and identified. 5. Our investigation of trimer and tetramer carboxylic acid metabolites of PCTFE has shown that the terminal carbon bearing two chlorine atoms is the exclusive site of oxidation. No evidence was found indicating oxidation of terminal carbon atoms having one chlorine.

Administration, Inhalation↗
PubMed1990

The interaction of orally administered iron with levodopa and methyldopa therapy.

The ability of methyldopa and levodopa to interact with both ferrous and ferric iron under a variety of conditions likely to be encountered physiologically has been examined. Spectrophotometric studies of ferrous sulphate in the presence of methyldopa indicate that no complexation occurs below pH2, whilst between pH 4-9, a variety of iron-methyldopa complexes is formed. The formation of these complexes is fast at high pH (pH 9: t1/2 less than 5 s), whilst the rate slows as the pH is lowered (pH 4: t1/2 greater than 30 min). These complexes are characteristic of iron-catecholate species, indicating that in the presence of methyldopa (and levodopa) ferrous iron undergoes autoxidation to the ferric form. The tight binding of ferric iron to methyldopa is predicted to alter the biodistribution characteristics of the complex with respect to the unchelated components. Furthermore, under the acid conditions of the stomach, redox cycling can occur. This will result in both catechol oxidation and production of the toxic hydroxyl radical. The findings suggest that care should be exercised when simultaneous administration of either methyldopa or levodopa with ferrous sulphate is indicated.

Administration, Oral↗
PubMed1981

The development of a regional scheme for preregistration training in hospital.

The development of a rational and comprehensive training scheme for preregistration graduate pharmacists in a metropolitan health region is described. The conceptual basis is an analysis of requirements of the training in terms of training theory, supported by detailed surveys. These are applied to produce an integrated scheme involving: a practical checklist, study days; self-assessment; monitoring, assessment and appraisal; and the training of responsible pharmacists.

Education, Pharmacy↗